Genetic variation is present in natural populations of essentially all animals, including humans. Studying the evolutionary processes acting on this variation is an important aspect of basic genetics research. The proposed work will address two issues. First, what is the evolutionary explanation for the correlation between heterozygosity and recombination in the Drosophila genome (Begun and Aquandro 1992, 1993)? Second, how does recombination rate, sex linkage, and chromosomal location affect protein evolution within and between species? Despite recent success in discovering how variation is distributed in natural populations, we are only just beginning to understand the forces that cause these patterns. Our view of the different patterns of genetic variation on the X-chromosome and autosomes within and between species, and of the role of linkage and selection in determining silent variation and protein variation in these species is really based on data from only a few genes. Our knowledge patterns of protein variation within species is especially poor. With the exception of a few genes, the primary data for population genetics are still from starch gel electrophoresis. Generalizations from such data are dubious. The evolutionary forces driving protein evolution between species are similarly obscure. The data I propose to collect are specifically aimed toward filling these gaps. They will take the form of DNA sequences from small population samples of Drosophila simulans and its close relative, melanogaster. I propose to measure silent heterozygosity and amino acid heterozygosity at approximately 100 different genes located in defined chromosomal regions. The data are likely to significantly refine our understanding of population genetics at several levels. They will contribute to our attempts to determine whether deleterious mutants are a significant factor in shaping patterns of variation across the entire genome. They will contribute to our understanding of the similarities and differences between evolutionary processes on the X chromosome and the autosomes. Finally, the data will contribute to our attempts to understand the different evolutionary processes acting on amino acid and silent variation in two closely related species.